NM_001370259.2(MEN1):c.660G>A (p.Trp220Ter) AND Multiple endocrine neoplasia, type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 21, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001224068.8

Allele description [Variation Report for NM_001370259.2(MEN1):c.660G>A (p.Trp220Ter)]

NM_001370259.2(MEN1):c.660G>A (p.Trp220Ter)

Gene:

MEN1:menin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.1

Genomic location:

Preferred name:

NM_001370259.2(MEN1):c.660G>A (p.Trp220Ter)

HGVS:

NC_000011.10:g.64807675C>T
NG_008929.1:g.8620G>A
NG_033040.1:g.567G>A
NM_000244.4:c.675G>A
NM_001370251.2:c.660G>A
NM_001370259.2:c.660G>AMANE SELECT
NM_001370260.2:c.660G>A
NM_001370261.2:c.660G>A
NM_001370262.2:c.555G>A
NM_001370263.2:c.555G>A
NM_130799.3:c.660G>A
NM_130800.3:c.675G>A
NM_130801.3:c.675G>A
NM_130802.3:c.675G>A
NM_130803.3:c.675G>A
NM_130804.3:c.675G>A
NP_000235.3:p.Trp225Ter
NP_001357180.2:p.Trp220Ter
NP_001357188.2:p.Trp220Ter
NP_001357189.2:p.Trp220Ter
NP_001357190.2:p.Trp220Ter
NP_001357191.2:p.Trp185Ter
NP_001357192.2:p.Trp185Ter
NP_570711.1:p.Trp220Ter
NP_570711.2:p.Trp220Ter
NP_570712.2:p.Trp225Ter
NP_570713.2:p.Trp225Ter
NP_570714.2:p.Trp225Ter
NP_570715.2:p.Trp225Ter
NP_570716.2:p.Trp225Ter
LRG_509t2:c.660G>A
LRG_509:g.8620G>A
LRG_509p2:p.Trp220Ter
NC_000011.9:g.64575147C>T
NM_130799.2:c.660G>A

Protein change:

W185*

Links:

dbSNP: rs886039414

NCBI 1000 Genomes Browser:

rs886039414

Molecular consequence:

NM_000244.4:c.675G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001370251.2:c.660G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001370259.2:c.660G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001370260.2:c.660G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001370261.2:c.660G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001370262.2:c.555G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001370263.2:c.555G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_130799.3:c.660G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_130800.3:c.675G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_130801.3:c.675G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_130802.3:c.675G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_130803.3:c.675G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_130804.3:c.675G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Multiple endocrine neoplasia, type 1 (MEN1)
Synonyms:: MEA I; MEN I; Endocrine adenomatosis multiple; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007540; MeSH: D018761; MedGen: C0025267; Orphanet: 652; OMIM: 131100

Recent activity

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Homo sapiens RAB, member RAS oncogene family-like 5 (RABL5), mRNA
Homo sapiens RAB, member RAS oncogene family-like 5 (RABL5), mRNA
gi|12232462|ref|NM_022777.1|

Nucleotide
AL884872 XGC-egg Xenopus tropicalis cDNA clone TEgg014h13 3', mRNA sequence
AL884872 XGC-egg Xenopus tropicalis cDNA clone TEgg014h13 3', mRNA sequence
gi|38676135|gnl|dbEST|20706310|emb| 872.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001396245	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 21, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17853334, 9709921, 12112656, 15635078, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001396245

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 21, 2020)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Developing effective screening strategies in multiple endocrine neoplasia type 1 (MEN 1) on the basis of clinical and sequencing data of German patients with MEN 1.

Schaaf L, Pickel J, Zinner K, Hering U, Höfler M, Goretzki PE, Spelsberg F, Raue F, von zur Mühlen A, Gerl H, Hensen J, Bartsch DK, Rothmund M, Schneyer U, Dralle H, Engelbach M, Karges W, Stalla GK, Höppner W.

Exp Clin Endocrinol Diabetes. 2007 Sep;115(8):509-17.

PubMed [citation]

PMID:: 17853334

Mutation analysis of the MEN1 gene in multiple endocrine neoplasia type 1, familial acromegaly and familial isolated hyperparathyroidism.

Teh BT, Kytölä S, Farnebo F, Bergman L, Wong FK, Weber G, Hayward N, Larsson C, Skogseid B, Beckers A, Phelan C, Edwards M, Epstein M, Alford F, Hurley D, Grimmond S, Silins G, Walters M, Stewart C, Cardinal J, Khodaei S, Parente F, et al.

J Clin Endocrinol Metab. 1998 Aug;83(8):2621-6.

PubMed [citation]

PMID:: 9709921

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001396245.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MEN1 are known to be pathogenic (PMID: 12112656, 17853334). A different variant (c.659G>A) giving rise to the same protein effect observed here (p.Trp220*) has been determined to be pathogenic (PMID: 9709921). This suggests that this variant is also likely to be causative of disease. This variant has been observed in individuas affected with multiple endocrine neoplasia type 1 (PMID: 12112656, 15635078). ClinVar contains an entry for this variant (Variation ID: 265235). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp220*) in the MEN1 gene. It is expected to result in an absent or disrupted protein product.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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